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Novel treatment for neuroblastoma by using live-attenuated poliovirus

Research Project

Project/Area Number 18K07817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionMie University

Principal Investigator

Toyoda Hidemi  三重大学, 医学系研究科, 准教授 (60525327)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords神経芽腫 / ポリオウイルス
Outline of Final Research Achievements

We have demonstrated that neuroblastoma (NB) subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of poliovirus (PV). Our results also suggested that the in vivo destruction of NB cells by virotherapy lead to a robust antitumor immune response. Since we used CD155-transfected NB for experiments, CD155 might be a target for antitumor immune response. Although NB can grow in naive mice, no tumor growth was observed in mice cured of NB that were reinnoculated with NB cells. Splenocytes harvested from NB-bearing mice treated with PV exhibited higher lytic activity against NB cells than did those from splenocytes derived from naive mice. In vitro T-cell depletion experiments indicated that CD8+ T cells were essential for the cytotoxic antitumor activity of splenocytes.

Academic Significance and Societal Importance of the Research Achievements

ポリオウイルスに感染した腫瘍細胞が抗腫瘍免疫を誘導することを証明できれば、ポリオウイルスで細胞死を誘導した腫瘍細胞を将来がんワクチンとして使用できる可能性も広がります。さらにマイクロアレイを用いて抗腫瘍免疫誘導の原因遺伝子が同定できれば、その遺伝子のコードするタンパクをがんワクチンの抗原として使用することも可能になり、またCAR-T療法の応用につながります。さらに、ポリオウイルスは神経芽腫だけでなく脳腫瘍を初めとする他の固形腫瘍にも細胞死を誘導することが知られているため、神経芽腫の治療だけでなく脳腫瘍など他の難治性小児がんの治療への臨床応用が可能な研究成果です。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2018

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Anti-tumor effect of Huaier extract against neuroblastoma cells in vitro2021

    • Author(s)
      Xu Dong-qing、Yuan Xiao-jun、Toyoda Hidemi、Hirayama Masahiro
    • Journal Title

      International Journal of Medical Sciences

      Volume: 18 Issue: 4 Pages: 1015-1023

    • DOI

      10.7150/ijms.48219

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Huaier Extract Induces Apoptosis in Hepatoblastoma Cells Via the MEK/ERK Signaling Pathway2020

    • Author(s)
      XU DONG-QING、YUAN XIAO-JUN、HIRAYAMA MASAHIRO、TOYODA HIDEMI
    • Journal Title

      In Vivo

      Volume: 34 Issue: 5 Pages: 2381-2388

    • DOI

      10.21873/invivo.12051

    • Related Report
      2020 Annual Research Report
  • [Journal Article] FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan Children’s Cancer Group2020

    • Author(s)
      Kumamoto Tadashi、Goto Hiroaki、Ogawa Chitose、Hori Toshinori、Deguchi Takao、Araki Takuya、Saito Akiko M.、Manabe Atsushi、Horibe Keizo、Toyoda Hidemi
    • Journal Title

      International Journal of Hematology

      Volume: 112 Issue: 5 Pages: 720-724

    • DOI

      10.1007/s12185-020-02962-2

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Refractory Ileal Perforations in a Cytomegalovirus-Infected Premature Neonate Resolved After Ganciclovir Therapy.2020

    • Author(s)
      Morimoto M, Sawada H, Yodoya N, Ohashi H, Toriyabe K, Hanaki R, Sugiura K, Toyoda H, Matsushita K, Koike Y, Otake K, Inoue M, Uchida K, Imai H, Mitani Y, Maruyama K, Komada Y, Ikeda T, Hirayama M.
    • Journal Title

      Front Pediatr.

      Volume: 8

    • DOI

      10.3389/fped.2020.00352

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Report of 2 Pediatric Cases With Li-Fraumeni Syndrome Related Malignancy in a Family2020

    • Author(s)
      Takeoka Mami、Toyoda Hidemi、Hirayama Junya、Suzuki Naofumi、Hanaki Ryo、Amano Keishiro、Iwamoto Shotaro、Hirayama Masahiro
    • Journal Title

      Journal of Pediatric Hematology/Oncology

      Volume: - Issue: 4 Pages: e567-e570

    • DOI

      10.1097/mph.0000000000001862

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo2018

    • Author(s)
      Xu Dong-Qing、Toyoda Hidemi、Yuan Xiao-Jun、Qi Lei、Chelakkot Vipin Shankar、Morimoto Mari、Hanaki Ryo、Kihira Kentarou、Hori Hiroki、Komada Yoshihiro、Hirayama Masahiro
    • Journal Title

      Exp Cell Res.

      Volume: 365 Issue: 2 Pages: 177-184

    • DOI

      10.1016/j.yexcr.2018.02.032

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Induction of MEK/ERK activity by AZD8055 confers acquired resistance in neuroblastoma2018

    • Author(s)
      Xu Dong-qing、Toyoda Hidemi、Qi Lei、Morimoto Mari、Hanaki Ryo、Iwamoto Shotaro、Komada Yoshihiro、Hirayama Masahiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 499 Issue: 3 Pages: 425-432

    • DOI

      10.1016/j.bbrc.2018.03.143

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical manifestation of patients with atypical hemolytic uremic syndrome with the C3 p.I1157T variation in the Kinki region of Japan.2018

    • Author(s)
      Matsumoto T, Toyoda H, Amano K, Hirayama M, Ishikawa E, Fujimoto M, Ito M, Ohishi K, Katayama N, Yoshida Y, Matsumoto M, Kawamura N, Ikejiri M, Kawakami K, Miyata T, Wada H
    • Journal Title

      Clin Appl Thromb Hemost

      Volume: 24 Issue: 8 Pages: 1301-1307

    • DOI

      10.1177/1076029618771750

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Weekly Rituximab Followed by Monthly Rituximab Treatment for Autoimmune Disease Associated With RAS-associated Autoimmune Leukoproliferative Disease2018

    • Author(s)
      Toyoda Hidemi、Deguchi Takao、Iwamoto Shotaro、Kihira Kentaro、Hori Hiroki、Komada Yoshihiro、Hirayama Masahiro
    • Journal Title

      Journal of Pediatric Hematology/Oncology

      Volume: 40 Issue: 8 Pages: e516-e518

    • DOI

      10.1097/mph.0000000000001276

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD3+ B-1a Cells as a Mediator of Disease Progression in Autoimmune-Prone Mice2018

    • Author(s)
      Yamamoto Wakako、Toyoda Hidemi、Xu Dong-qing、Hanaki Ryo、Morimoto Mari、Nakato Daisuke、Ito Takahiro、Iwamoto Shotaro、Bonno Motoki、Tanaka Shigeki、Hirayama Masahiro
    • Journal Title

      Mediators of Inflammation

      Volume: 2018 Pages: 1-10

    • DOI

      10.1155/2018/9289417

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 自己免疫疾患モデルマウスにおけるCD3陽性B-1a細胞の意義2018

    • Author(s)
      1.山本 和歌子, 豊田 秀実, 花木 良, 森本 真理, 中藤 大輔, 伊藤 卓洋, 平山 雅浩
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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